Capping protein regulator and myosin 1 linker 3 regulates transcription of key cytokines in activated phagocytic cells.
Cell Signal
; 78: 109848, 2021 02.
Article
en En
| MEDLINE
| ID: mdl-33246003
ABSTRACT
We have recently reported that capping protein regulator and myosin 1 linker 3 (CARMIL3), first identified as an oncofetal-like gene, is required for metastasis of breast and prostate cancer cells via regulating the actin cytoskeletal dynamics near the plasma membrane. Here, we demonstrate a novel function of CARMIL3 as an essential regulator of the transcription of several key proinflammatory cytokines in macrophages engulfing apoptotic cells and/or exposed to lipopolysaccharides (LPS). CARMIL3-deficient macrophages expressed strongly abrogated levels of interleukin (IL)-6, TNF-α, IL-1ß and IL-23 in response to LPS, whereas IL-10 expression was enhanced. An RNA-seq analysis of CARMIL3-deficient and wild-type (WT) RAW264.7 cells stimulated with LPS revealed many differentially expressed genes, impacting several important inflammatory pathways. At the molecular level, CARMIL3 deficiency caused a strong impairment in LPS-activated nuclear factor-κB (NF-κB) signaling with decreased IKKα/ß and IκBα phosphorylation and severely reduced p65 protein levels. This study uncovers a crucial role of CARMIL3 in impacting the balance between inflammation and tissue homeostasis via regulating major cytokines production in phagocytic cells.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Transcripción Genética
/
Transducción de Señal
/
Citocinas
/
Macrófagos
/
Proteínas de Microfilamentos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Cell Signal
Año:
2021
Tipo del documento:
Article
País de afiliación:
China